The central goal of this proposed research is to design, test and deploy a novel, compact, clinically robust measurement platform capable of determining intrinsic optical properties and chromophore concentrations of in-vivo skin across a broad spectral range. The resulting technique, known as Spatially Modulated Quantitative Spectroscopy (SMoQS) is based on the principles of Spatial Frequency Domain Imaging, which has been an area of considerable work in our lab. The targeted application of this proposal is the quantitative characterization of suspicious lesions that have the clinical appearance of melanoma. Melanoma is a highly curable disease when detected early, yet it remains the deadliest form of skin cancer;responsible for more than 80% of all skin cancer death. This statistic illustrates the large gap in technological development for a robust method of early detection. A non-invasive technology that can quantitatively detect chemical and structural properties in a depth sensitive manner will have significant impact on both the efficiency and effectiveness of the screening process. Because SMoQS can accommodate full-spectrum data, it can quantify melanin, water, hemoglobin concentration and oxygenation and structural information. SMoQS is well suited to enabling detailed collection of in-vivo functional and structural information, resulting in an opportunity for comprehensive characterization of suspicious lesions. Additionally, with appropriate models, SMoQS is capable of quantifying optical properties and chromophore concentrations of tissue in a depth resolved manner. Previous investigations by other groups have indicated that key discriminatory features of disease states may manifest in subtle spectral changes, alterations to the structure and composition of specific chemical species [2, 3]. Broad spectral measurements such as those enabled by the method that we propose are necessary to capture and characterize these subtle features. Progression of disease occurs in a depth-wise manner, depth sensitive measurements thus confer an advantage with respect to identifying the severity of the disease in-vivo. Within the context of this proposal, we will build a bench top system to optimize and evaluate SMoQS in terms of measurement accuracy and clinical performance. Results from proof of principle experiments are included in this application as a demonstration of the fundamental capabilities of this technique to faithfully extract quantitative optical properties from turbid media. We will advance existing models and data analysis methods towards improved, quantitative depth resolution capabilities of optical properties specific to the milieu of in-vivo skin imaging. Lastly, we will use the insight and knowledge gained from these two steps to build a clinically robust SMoQS instrument that will be inserted into two existing IRB approved studies that are oriented around imaging of various skin pathologies with a particular thrust toward improved understanding of functional and structural aspects of melanoma that are accessible via optics. PUBLIC HEALTH RELEVANCE: Malignant melanoma is the deadliest form of skin cancer, responsible for over 80% of all skin cancer deaths, yet, early detection and proper treatment allows for 95% cure rate. Currently, a technological gap exists in accurate and efficient techniques that may identify the disease in its early stages and significantly improve patient outcomes and reduce health care cost burdens due to the high percentage of precautionary, yet unnecessary, tissue biopsies. We propose to design, build, and test and deploy a new optical device that will enable us to gather depth resolved information about blood content, water content, structural changes and melanin concentration for skin lesions, including melanoma, and ultimately it is our hope that such a device may eventually be used to improve the management of skin cancer.